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Targeting Wnts at the source--new mechanisms, new biomarkers, new drugs.

Publication ,  Journal Article
Madan, B; Virshup, DM
Published in: Mol Cancer Ther
May 2015

Wnt signaling is dysregulated in many cancers and is therefore an attractive therapeutic target. The focus of drug development has recently shifted away from downstream inhibitors of β-catenin. Active inhibitors of Wnt secretion and Wnt/receptor interactions have been developed that are now entering clinical trials. Such agents include inhibitors of Wnt secretion, as well as recombinant proteins that minimize Wnt-Frizzled interactions. These new therapies arrive together with the recent insight that cancer-specific upregulation of Wnt receptors at the cell surface regulates cellular sensitivity to Wnts. Loss-of-function mutations in RNF43 or ZNRF3 and gain-of-function chromosome translocations involving RSPO2 and RSPO3 are surprisingly common and markedly increase Wnt/β-catenin signaling in response to secreted Wnts. These mutations may be predictive biomarkers to select patients responsive to newly developed upstream Wnt inhibitors.

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Published In

Mol Cancer Ther

DOI

EISSN

1538-8514

Publication Date

May 2015

Volume

14

Issue

5

Start / End Page

1087 / 1094

Location

United States

Related Subject Headings

  • Wnt Signaling Pathway
  • Oncology & Carcinogenesis
  • Neoplasms
  • Mutation
  • Humans
  • Drug Design
  • Clinical Trials as Topic
  • Biomarkers, Tumor
  • Antineoplastic Agents
  • Animals
 

Citation

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Madan, B., & Virshup, D. M. (2015). Targeting Wnts at the source--new mechanisms, new biomarkers, new drugs. Mol Cancer Ther, 14(5), 1087–1094. https://doi.org/10.1158/1535-7163.MCT-14-1038
Madan, Babita, and David M. Virshup. “Targeting Wnts at the source--new mechanisms, new biomarkers, new drugs.Mol Cancer Ther 14, no. 5 (May 2015): 1087–94. https://doi.org/10.1158/1535-7163.MCT-14-1038.
Madan B, Virshup DM. Targeting Wnts at the source--new mechanisms, new biomarkers, new drugs. Mol Cancer Ther. 2015 May;14(5):1087–94.
Madan, Babita, and David M. Virshup. “Targeting Wnts at the source--new mechanisms, new biomarkers, new drugs.Mol Cancer Ther, vol. 14, no. 5, May 2015, pp. 1087–94. Pubmed, doi:10.1158/1535-7163.MCT-14-1038.
Madan B, Virshup DM. Targeting Wnts at the source--new mechanisms, new biomarkers, new drugs. Mol Cancer Ther. 2015 May;14(5):1087–1094.

Published In

Mol Cancer Ther

DOI

EISSN

1538-8514

Publication Date

May 2015

Volume

14

Issue

5

Start / End Page

1087 / 1094

Location

United States

Related Subject Headings

  • Wnt Signaling Pathway
  • Oncology & Carcinogenesis
  • Neoplasms
  • Mutation
  • Humans
  • Drug Design
  • Clinical Trials as Topic
  • Biomarkers, Tumor
  • Antineoplastic Agents
  • Animals